ACTH-induced cortisol secretion is mediated by cAMP and PKC in various adrenocortical adenomas.
We examined the role of PKC in cortisol secretion from adrenocortical adenomas. Isolated cells were prepared from aldosterone producing adenoma (APA, n=5), APA complicated with pre-clinical Cushing's syndrome (APA+PC, n=1), PC (n=2), and cortisol producing adenoma (CPA, n=5). They were stimulated with 100 nM ACTH, 1 microM forskolin (FS), 1 microM tetradecanoyl phorbol 13-acetate (TPA), and 100 nM angiotensin II (AngII). ACTH was most potent to secret cortisol. FS also stimulated cortisol secretion, but did less-potently. TPA and AngII also stimulated cortisol secretion significantly in cells from CPA. Furthermore, ACTH- and TPA-induced PKCalpha and beta translocations from cytosol to membrane were observed in adenoma cells from APA+PC, PC, and CPA. In conclusion, it was suggested that ACTH-induced cortisol secretion may be mediated by both PKC and protein kinase A in adrenocortical adenomas, and that PKC-mediated signal transduction may be involved in ACTH-induced cortisol secretion in CPA.
Ishizuka
T
T
The Third Department of Internal Medicine, Gifu University School of Medicine, Japan.
Daidoh
H
H
Morita
H
H
Mune
T
T
Miura
A
A
Suwa
T
T
Shibata
T
T
Yamada
K
K
Itaya
S
S
Kajita
K
K
Yasuda
K
K
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003480:Cushing Syndrome / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D000804:Angiotensin II; D005576:Colforsin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone